This randomized study assessed if intravenous iron improves hemoglobin (Hb) response and permits decreased epoetin dose in anemic (Hb 9-11 g/dl), transfusion-independent patients with stainable iron in the bone marrow and lymphoproliferative malignancies not receiving chemotherapy. Patients (n ¼ 67) were randomized to subcutaneous epoetin beta 30 000 IU once weekly for 16 weeks with or without concomitant intravenous iron supplementation. There was a significantly (Po0.05) greater increase in mean Hb from week 8 onwards in the iron group and the percentage of patients with Hb increase X2 g/dl was significantly higher in the iron group (93%) than in the noiron group (53%) (per-protocol population; P ¼ 0.001). Higher serum ferritin and transferrin saturation in the iron group indicated that iron availability accounted for the Hb response difference. The mean weekly patient epoetin dose was significantly lower after 13 weeks of therapy (P ¼ 0.029) and after 15 weeks approximately 10 000 IU (425%) lower in the iron group, as was the total epoetin dose (P ¼ 0.051). In conclusion, the Hb increase and response rate were significantly greater with the addition of intravenous iron to epoetin treatment in iron-replete patients and a lower dose of epoetin was required.
In this double-blind, placebo-controlled study, 363 patients with untreated multiple myeloma were randomized to receive either melphalan-prednisone and thalidomide (MPT) or melphalan-prednisone and placebo (MP). The dose of melphalan was 0.25 mg/kg and prednisone was 100 mg given daily for 4 days every 6 weeks until plateau phase. The dose of thalidomide/ placebo was escalated to 400 mg daily until plateau phase and thereafter reduced to 200 mg daily until progression. A total of 357 patients were analyzed. Partial response was 34% and 33%, and very good partial response or better was 23% and 7% in the MPT and MP arms, respectively (P < .001). There was no significant difference in progression-free or overall survival, with median survival being 29 months in the MPT arm and 32 months in the MP arm. Most quality of life outcomes improved equally in both arms, apart from constipation, which was markedly increased in the MPT arm. Constipation, neuropathy, nonneuropathy neurologic toxicity, and skin reactions were significantly more frequent in the MPT arm. The number of thromboembolic events was equal in the 2 treatment arms. In conclusion, MPT had a significant antimyeloma effect, but this did not translate into improved survival. This trial was
Associations with functional groups of natural organic matter (NOM) are of great importance for bioavailability, toxicity, and mobility of trace metals in soils and waters. In this study, the coordination chemistry of copper, Cu(ll), in organic soils and dissolved organic matter (DOM) from soils and streams was investigated by extended X-ray absorption fine structure (EXAFS) spectroscopy. In both soil organic matter (SOM) and DOM (990-11 000 microg Cu g(-1) dryweight, pH 2.8-6.3), Cu(ll) was coordinated by 4 oxygen/ nitrogen (O/N) atoms at a distance of 1.92-1.95 angstroms in the first coordination shell. These four atoms are positioned in the equatorial plane of a Jahn-Teller distorted octahedron. In samples with a pH of 4.8-6.3, a second coordination shell with 2.0-3.8 C atoms was located at a distance of 2.76-2.86 angstroms. A significant improvement (19-39%) of the fit was obtained by including a third coordination shell with 2.0-3.8 O/C atoms involved in single scattering at an average distance of 3.69 angstroms and multiple scattering at an average distance of 4.19 angstroms. Our results provide evidence for inner-sphere complexation of Cu(ll) in NOM and suggest that Cu(ll) is complexed by either one or two five-membered chelate rings involving possible combinations of amino, carboxyl, or carbonyl functional groups. Ion activity measurements showed that less than 0.2% of total Cu was in the form of free Cu2+ in our samples at pH 4.8-6.3.
Despite methylmercury (MeHg) production in boreal wetlands being a research focus for decades, little is known about factors in control of methylation and demethylation rates and the effect of wetland type. This is the first study reporting potential Hg methylation (k m ) and MeHg demethylation rate constants (k d ) in boreal wetland soils. Seven wetlands situated in northern and southern Sweden were characterized by climatic parameters, nutrient status (e.g. type of vegetation, pH, C/N ratio, specific UV-absorption), iron and sulfur biogeochemistry. Based on nutrient status, the wetlands were divided into three groups; (I) three northern, nutrient poor fens, (II) a nutrient gradient ranging from an ombrotrophic bog to a fen with intermediate nutrient status, and (III) southern, more nutrient rich sites including two mesotrophic wetlands and one alder (Alnus) forest swamp. The k m /k d ratio in general followed %MeHg in soil and both measures were highest at the fen site with intermediate nutrient status. Northern nutrient poor fens and the ombrotrophic bog showed intermediate values of %MeHg and k m /k d . The two mesotrophic wetlands showed the lowest %MeHg and k m /k d , whereas the alder swamp had high k m and k d , resulting in an intermediate k m /k d and %MeHg. Molybdate addition experiments suggest that net MeHg production was mainly caused by the activity of sulfate reducing bacteria. A comparison with other studies, show that k m and %MeHg in boreal freshwater wetlands in general are higher than in other environments. Our results support previous suggestions that the highest MeHg net production in boreal landscapes is to be found in fens with an intermediate nutrient status.
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